While neutrophils are an important component of innate immunity, they are also capable of causing tissue destruction, largely due to the oxidative burst of activated cells. Thus, it is beneficial to tightly control neutrophil activation. The CXC chemokine KC, a functional orthologue of human IL-8, is bound to the basal epithelial cell surface via syndecan-1. This KC/syndecan-1 complex is shed from the cell surface by matrilysin produced by epithelial cells in response to injury. We propose that the KC/syndecan-1 complex prevents neutrophil activation when it is cell membrane-associated, yet promotes neutrophil activation when it is shed by matrilysin from the cell surface. To investigate this, we will assess the activation state of neutrophils in matrilysin-null mouse lungs and BALF, and compare it to those from wild-type mice in acute stages of bleomycin lung injury. We will also utilize an air-liquid interface tracheal epithelial transwell culture system to determine if neutrophil response differs between membrane-bound and soluble KC/syndecan-1 complexes. This project should provide novel insights into the activation of neutrophils at the epithelial surface of the lungs, as well as in other tissues. [unreadable] [unreadable] [unreadable]